The Effect of Calcium Channel Antagonists on Spontaneous and Evoked Epileptiform Activity in the Rat Neocortex In Vitro

Calcium influx through voltage-activated calcium channels may play a crucial role in the propagation and maintenance of seizure activity. We have examined the contribution of various types of calcium currents to epileptogenesis by studying the effects of various calcium channel blockers on epileptiform activity. N-methyl-d-aspartate receptor-mediated epileptiform activity was induced by removal of magnesium ions superfusing the cortex, or by low-frequency stimulation of the underlying white matter. CoCl2, CdCl2 and omega-conotoxin, acting at the N- and L-type calcium channels, significantly reduced epileptiform activity. L-channel antagonists nifedipine and verapamil, and the agonist BAY K 8644, increased spontaneous bursting in cortical wedges, but had no effect upon evoked activity. The T-channel blocker NiCl2 had variable effects on epileptiform activity, whereas phenytoin consistently reduced such activity. These results suggest that calcium influx underlying epileptiform activity in the rat neocortex may occur at least partially via the activation of the N-type calcium channel. However, contributions from other calcium channel types cannot be excluded.     

Community absorption of the mentally ill: The new challenge

In 1975, twelve years after enactment of the Community Mental Health Centers Act, we find one of the greatest obstacles to fulfillment of our hopes to be pervasive hostility to acceptance of the mentally ill in many communities. The River Region Program has hurdled this obstacle by breaking the artificially large mental health catchment areas into manageable segments of 16 smaller service areas close to the people it serves in seven counties of Kentucky. In each of these service areas it has involved a broad spectrum of citizens in the planning of every service. All of this is of particular relevance today in light of the Supreme Court's D,onaldson decision, that mentally ill persons cannot be confined involuntarily if they are not dangerous and can live safely in the outside world. The outside world must be prepared to receive these people, and we in the mental health field must do our job in this vital preparation.Mr. Gorman originally presented this paper as a speech at the Annual Dinner, of the River Region Mental Health — Mental Retardation Board in Louisville, Kentucky, on June 20, 1975.     

Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies.

PURPOSE: Recently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study. PATIENTS AND METHODS: Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting level of approximately 130 micromol/L to below the level of detection (< 2 micromol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose. RESULTS: This therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present (> 680 days). CONCLUSION: Elimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted.     

A longitudinal,functional study of peripheral nerve recovery in the mouse

Objectives: To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. Study Design: Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. Results: Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). Conclusions: The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.     

2005年北京国际糖尿病足及其相关疾病论坛专题痛性糖尿病神经病变

3.3 糖尿病慢性感觉-运动神经病变的流行病学 糖尿病神经病变的流行病学和自然病程尚不完全清楚，主要原因是在不同的研究中应用不同的定义和诊断标准，缺乏查证资料和基于人群的临床研究。慢性感觉运动神经病变常见并且是糖尿病患者晚期的重要并发症。Kumar等人的研究显示，40％的2型糖尿病患者存在神经病变缺陷，而不足一半的患者有神经病变的相关症状。     

Positron emission tomography for target volume definition in the treatment of non-small cell lung cancer.

The additional benefit of positron emission tomography (PET) in the initial staging of non-small cell lung cancer (NSCLC) has generated interest in 18F-fluorodeoxyglucose (FDG) PET as a means of defining the extent of primary lung tumour for radiotherapy treatment planning (RTP). A review of published data suggests that PET results in a reduction in the CT-derived GTV for NSCLC primary target volume in 15% of the patients. This is principally due to the ability of PET to distinguish tumour from atelectasis. However, the difficulty of tumour edge definition, limited spatial resolution and tumour motion during image acquisition currently limits the accuracy of PET in target volume delineation in NSCLC without adjacent lung consolidation. This is compounded by the lack of data correlating PET with spatial pathology at the primary tumour site. With the current technical limitations, it is not established that PET can add accuracy to the CT-defined primary target delineation in RTP of NSCLC. It is hoped that advances in PET and combined PET/CT imaging may overcome some of the technical limitations. Future use of PET for primary tumour delineation in NSCLC will also be critically dependent on the detailed studies of imaging-pathology correlation.